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Hypoxic Preconditioning with Cobalt of Bone Marrow Mesenchymal Stem Cells Improves Cell Migration and Enhances Therapy for Treatment of Ischemic Acute Kidney Injury

Mesenchymal stem cell (MSC) administration is known to enhance the recovery of the kidney following injury. Here we tested the potential of hypoxic-preconditioned-MSC transplantation to enhance the efficacy of cell therapy on acute kidney injury (AKI) by improving MSC migration to the injured kidney...

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Autores principales: Yu, Xiaofang, Lu, Chunlai, Liu, Hong, Rao, Shengxiang, Cai, Jieru, Liu, Shaopeng, Kriegel, Alison J., Greene, Andrew S., Liang, Minyu, Ding, Xiaoqiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3650042/
https://www.ncbi.nlm.nih.gov/pubmed/23671625
http://dx.doi.org/10.1371/journal.pone.0062703
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author Yu, Xiaofang
Lu, Chunlai
Liu, Hong
Rao, Shengxiang
Cai, Jieru
Liu, Shaopeng
Kriegel, Alison J.
Greene, Andrew S.
Liang, Minyu
Ding, Xiaoqiang
author_facet Yu, Xiaofang
Lu, Chunlai
Liu, Hong
Rao, Shengxiang
Cai, Jieru
Liu, Shaopeng
Kriegel, Alison J.
Greene, Andrew S.
Liang, Minyu
Ding, Xiaoqiang
author_sort Yu, Xiaofang
collection PubMed
description Mesenchymal stem cell (MSC) administration is known to enhance the recovery of the kidney following injury. Here we tested the potential of hypoxic-preconditioned-MSC transplantation to enhance the efficacy of cell therapy on acute kidney injury (AKI) by improving MSC migration to the injured kidney. Cobalt was used as hypoxia mimetic preconditioning (HMP). MSC were subjected to HMP through 24 h culture in 200 µmol/L cobalt. Compared to normoxia cultured MSC (NP-MSC), HMP significantly increased the expression of HIF-1α and CXCR4 in MSC and enhanced the migration of MSC in vitro. This effect was lost when MSC were treated with siRNA targeting HIF-1α or CXCR4 antagonist. SPIO labeled MSC were administered to rats with I/R injury followed immediately by magnetic resonance imaging. Imaging clearly showed that HMP-MSC exhibited greater migration and a longer retention time in the ischemic kidney than NP-MSC. Histological evaluation showed more HMP-MSC in the glomerular capillaries of ischemic kidneys than in the kidneys receiving NP-MSC. Occasional tubules showed iron labeling in the HMP group, while no tubules had iron labeling in NP group, indicating the possibility of tubular transdifferentiation after HMP. These results were also confirmed by fluorescence microscopy study using CM-DiI labeling. The increased recruitment of HMP-MSC was associated with reduced kidney injury and enhanced functional recovery. This effect was also related to the increased paracrine action by HMP-MSC. Thus we suggest that by enhancing MSC migration and prolonging kidney retention, hypoxic preconditioning of MSC may be a useful approach for developing AKI cell therapy.
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spelling pubmed-36500422013-05-13 Hypoxic Preconditioning with Cobalt of Bone Marrow Mesenchymal Stem Cells Improves Cell Migration and Enhances Therapy for Treatment of Ischemic Acute Kidney Injury Yu, Xiaofang Lu, Chunlai Liu, Hong Rao, Shengxiang Cai, Jieru Liu, Shaopeng Kriegel, Alison J. Greene, Andrew S. Liang, Minyu Ding, Xiaoqiang PLoS One Research Article Mesenchymal stem cell (MSC) administration is known to enhance the recovery of the kidney following injury. Here we tested the potential of hypoxic-preconditioned-MSC transplantation to enhance the efficacy of cell therapy on acute kidney injury (AKI) by improving MSC migration to the injured kidney. Cobalt was used as hypoxia mimetic preconditioning (HMP). MSC were subjected to HMP through 24 h culture in 200 µmol/L cobalt. Compared to normoxia cultured MSC (NP-MSC), HMP significantly increased the expression of HIF-1α and CXCR4 in MSC and enhanced the migration of MSC in vitro. This effect was lost when MSC were treated with siRNA targeting HIF-1α or CXCR4 antagonist. SPIO labeled MSC were administered to rats with I/R injury followed immediately by magnetic resonance imaging. Imaging clearly showed that HMP-MSC exhibited greater migration and a longer retention time in the ischemic kidney than NP-MSC. Histological evaluation showed more HMP-MSC in the glomerular capillaries of ischemic kidneys than in the kidneys receiving NP-MSC. Occasional tubules showed iron labeling in the HMP group, while no tubules had iron labeling in NP group, indicating the possibility of tubular transdifferentiation after HMP. These results were also confirmed by fluorescence microscopy study using CM-DiI labeling. The increased recruitment of HMP-MSC was associated with reduced kidney injury and enhanced functional recovery. This effect was also related to the increased paracrine action by HMP-MSC. Thus we suggest that by enhancing MSC migration and prolonging kidney retention, hypoxic preconditioning of MSC may be a useful approach for developing AKI cell therapy. Public Library of Science 2013-05-09 /pmc/articles/PMC3650042/ /pubmed/23671625 http://dx.doi.org/10.1371/journal.pone.0062703 Text en © 2013 Yu et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Yu, Xiaofang
Lu, Chunlai
Liu, Hong
Rao, Shengxiang
Cai, Jieru
Liu, Shaopeng
Kriegel, Alison J.
Greene, Andrew S.
Liang, Minyu
Ding, Xiaoqiang
Hypoxic Preconditioning with Cobalt of Bone Marrow Mesenchymal Stem Cells Improves Cell Migration and Enhances Therapy for Treatment of Ischemic Acute Kidney Injury
title Hypoxic Preconditioning with Cobalt of Bone Marrow Mesenchymal Stem Cells Improves Cell Migration and Enhances Therapy for Treatment of Ischemic Acute Kidney Injury
title_full Hypoxic Preconditioning with Cobalt of Bone Marrow Mesenchymal Stem Cells Improves Cell Migration and Enhances Therapy for Treatment of Ischemic Acute Kidney Injury
title_fullStr Hypoxic Preconditioning with Cobalt of Bone Marrow Mesenchymal Stem Cells Improves Cell Migration and Enhances Therapy for Treatment of Ischemic Acute Kidney Injury
title_full_unstemmed Hypoxic Preconditioning with Cobalt of Bone Marrow Mesenchymal Stem Cells Improves Cell Migration and Enhances Therapy for Treatment of Ischemic Acute Kidney Injury
title_short Hypoxic Preconditioning with Cobalt of Bone Marrow Mesenchymal Stem Cells Improves Cell Migration and Enhances Therapy for Treatment of Ischemic Acute Kidney Injury
title_sort hypoxic preconditioning with cobalt of bone marrow mesenchymal stem cells improves cell migration and enhances therapy for treatment of ischemic acute kidney injury
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3650042/
https://www.ncbi.nlm.nih.gov/pubmed/23671625
http://dx.doi.org/10.1371/journal.pone.0062703
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